Development of hyaluronic acid-based nanocomposite eye drops: A synergistic platform for enhanced ocular delivery of acetazolamide

The limitations of conventional therapeutic approaches for treating ocular diseases such as glaucoma via the topical administration route are nowadays a constant challenge for researchers in the field of pharmaceutical technology. The present study shows the feasibility of developing nanocomposite hydrogel-based eye drops for the topical delivery of acetazolamide, underlining its potential benefits in the glaucoma treatment. In detail, hyaluronic acid hydrogels loaded with acetazolamide nanocrystals were developed and characterized in accordance with requirements for ocular administration. Nanocomposite hydrogels composition was optimized with hyaluronic acid 1.25% w / v and acetazolamide nanocrystals 5% w/v, showing a viscosity compatible with topical instillation (μ₀ < 30 mPa·s). Fourier-transform infrared spectroscopy and thermal analyses showed purely physical incorporation of the nanocrystals into the polymeric network. Microscopy analysis revealed a homogeneous morphology with uniform nanocrystal dispersion and no visible phase separation. Rheological characterization demonstrated enhanced mucoadhesive properties, attributed to physical entanglement between hyaluronic acid and mucin. In vitro release studies in simulated tear fluid showed a biphasic release profile with an initial burst followed by a sustained diffusion-controlled release over 72 h. In vivo studies in albino normotensive rabbits showed no signs of irritation or damage after topical ocular administration of nanocomposite hydrogels and demonstrated a significant reduction in intraocular pressure compared with normal saline solution, even at a low drug dose. Furthermore, the duration of the hypotensive effect tended to go beyond that of a commercial formulation tested as reference. Overall, the nanocomposite hydrogel emerges as a promising platform for ocular delivery of acetazolamide.